Deciphera Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, announced the presentation today of updated preliminary results from its ongoing Phase 1 clinical study of DCC-2618, the company's broad-spectrum KIT and PDGFRα inhibitor, in patients with gastrointestinal stromal tumors (GIST) as a proffered paper presentation at the European Society of Medical Oncology (ESMO) 2018 Congress in Munich, Germany.
"We are extremely pleased with the preliminary results presented today that we believe demonstrate the potential of DCC-2618 to provide improved, durable clinical benefit for GIST patients from second-line through fourth-line-plus," said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. "While the data set is still maturing, we believe the median progression free survival value of 42 weeks observed in second-line GIST patients strongly supports our planned randomized Phase 3 study, INTRIGUE, in second-line GIST patients, which we expect to initiate before the end of the year. In addition, the disease control rate and objective response rate observed with DCC-2618 in second-line GIST patients continues to exceed the values reported in previously published, centrally-read, registrational trials for sunitinib."
The presentation reported preliminary results with a cutoff date of August 31, 2018 that include investigator-assessed median progression free survival (mPFS), objective response rates by best response (ORR) and disease control rates at 3 months (DCR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 across 178 patients receiving DCC-2618 at doses of ≥100mg daily:
Notes: (1) Includes nine unconfirmed responses: 2nd line (n=1), 3rd line (n=3) and ≥4th line (n=5); (2) Does not reflect one PR reported after cutoff date, which would result in an ORR in 2nd line of 21% and an ORR in 2nd line and 3rd line combined of 22%; (3) Excludes five patients due to missing data at the time of data cutoff (n=2), lack of first tumor assessment (n=1), withdrawal of consent prior to first assessment (n=1) and unrelated death at C1D4 prior to first assessment (n=1); (4) 59 of 67 combined 2nd line and 3rd line patients received 150mg once daily; and (5) Censored patients for mPFS were 2nd line (58%), 3rd line (52%), 4th line and 4th line plus (35%) and 2nd and 3rd line (55%).
"The preliminary progression free survival data and objective response rates observed with DCC-2618 are very encouraging across all lines of therapy presented: second-, third-, and fourth-line and beyond," said Suzanne George, M.D., Director of Clinical Research, Center for Sarcoma and Bone Oncology and Senior Physician at the Dana Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School. "There is a clear unmet need for effective and well tolerated options for patients with metastatic GIST beyond the first-line."
Highlights from the proffered paper include:
Preliminary Clinical Activity in Second-, Third-, Fourth- and Fourth-Line-Plus GIST Patients Demonstrates the Potential for Durable Clinical Outcomes with DCC-2618
- Progression Free Survival (mPFS): The mPFS values observed with DCC-2618 were 42 weeks in second-line patients and 40 weeks in third-line patients. Previously published results for approved therapies from centrally-read registrational trials reported a mPFS for sunitinib of 24 weeks in second-line patients and a mPFS for regorafenib of 21 weeks in third-line patients. In fourth- and fourth-line-plus patients, where there are currently no approved therapies, the observed mPFS with DCC-2618 was 24 weeks. Published studies have reported a mPFS of 4-6 weeks for similarly heavily pre-treated patients who did not receive an active therapy.
- Disease Control Rate (DCR): The observed DCRs at three months of 79% in second-line patients and 83% in third-line patients exceed the previously published results for approved therapies from centrally-read registrational trials of 60% for sunitinib in second-line patients and 53% for regorafenib in third-line patients. The DCR observed for DCC-2618 in fourth-line and fourth-line-plus patients was 66%.
- Objective Response Rate (ORR): The observed ORRs of 18% in second-line patients and 24% in third-line patients continue to exceed the previously published results for approved therapies from centrally-read registrational trials of 7% for sunitinib in second-line patients and 5% for regorafenib in third-line patients. These values do not include a partial response in one second-line patient that was observed after the cutoff date, which would result in an ORR in second-line patients of 21%. The ORR observed for DCC-2618 in fourth-line and fourth-line-plus patients was 9%.
Prolonged Treatment Duration in GIST Patients Receiving DCC-2618 - Cutoff Date of August 31, 2018
- In the second-line cohort, as of the cutoff date, 17 patients received DCC-2618 at doses of ≥100mg daily for >6 months with 65% (11 of 17) of these patients remaining on study.
- In the third-line cohort, as of the cutoff date, 20 patients received DCC-2618 at doses of ≥100mg daily for >6 months with 75% (15 of 20) of these patients remaining on study.
- In the fourth-line and fourth-line-plus patients, as of the cutoff date, 46 patients received DCC-2618 at doses of ≥100mg daily for >6 months with 74% (34 of 46) of these patients remaining on study.
Updated Safety Data Continue to Demonstrate a Favorable Tolerability Profile for DCC-2618
- For 178 GIST patients treated at doses above ≥100mg daily, DCC-2618 was generally well tolerated.
- Among the treatment-emergent adverse events (TEAEs) reported by investigators (>10%), regardless of relationship to DCC-2618, the most common were: alopecia (50%), myalgia (44%), fatigue (43%), constipation (34%), hand-foot skin reaction (32%), nausea (30%), decreased appetite (28%), weight decreased (24%), abdominal pain (23%), diarrhea (23%) and lipase increase (23%).
- Among the 178 GIST patients treated at doses above ≥100mg daily:
- 14% (24) patients experienced dose reductions due to TEAE.
- 11% (19) experienced treatment discontinuations due to TEAE.